Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001258640
Ethics application status
Approved
Date submitted
24/08/2014
Date registered
2/12/2014
Date last updated
25/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized, double-blinded study investigating the safety and efficacy of daily low-dose oral fluconazole versus weekly fluconazole in the treatment of chronic vulvovaginal candidiasis
Scientific title
A randomized, double-blinded study investigating the safety and efficacy of daily low-dose oral fluconazole versus weekly fluconazole in patients with chronic vulvovaginal candidiasis
Secondary ID [1] 285214 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic vulvovaginal candidiasis 292833 0
Condition category
Condition code
Skin 293133 293133 0 0
Dermatological conditions
Infection 293917 293917 0 0
Other infectious diseases
Renal and Urogenital 293918 293918 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention:
Patients aged 18 years or older with chronic vulvovaginal candidiasis (as diagnosed using validated diagnostic criteria) will be recruited for the study through the vulval dermatology clinical at Royal North Shore Hospital. Patients will initially undergo clinical examination, low vaginal swab, and baseline blood tests (full blood count, electrolytes/urea/creatinine, and liver function tests). If the blood tests return normal, subjects will be randomised by an independent investigator into one of two groups. Intervention group will receive treatment of fluconazole 50mg orally daily for 12 weeks. Patients will complete a questionnaire grading their symptoms and objective signs (erythema, oedema, fissuring, distribution, discharge) will be assessed by 2 independent blinded doctors. Date of menstrual cycle will be recorded. Patients will be reviewed at 6 weeks of treatment. Response to treatment will be re-assessed using the same criteria. At week 12, all patients will undergo repeat clinical examination, questionnaire and blood tests. Those whose symptoms have resolved may continue on 50mg fluconazole twice per week, as an ongoing maintenance dose. These patients will be reassessed using all criteria at 3, 6 and 12 months follow up. The strategy used to monitor adherence to the intervention will be counting and documenting patient's drug tablet return.
Intervention code [1] 290089 0
Treatment: Drugs
Comparator / control treatment
Comparator:
Patients aged 18 years or older with chronic vulvovaginal candidiasis (as diagnosed using validated diagnostic criteria) will be recruited for the study through the vulval dermatology clinical at Royal North Shore Hospital. Patients will initially undergo clinical examination, low vaginal swab, and baseline blood tests (full blood count, electrolytes/urea/creatinine, and liver function tests). If the blood tests return normal, subjects will be randomised by an independent investigator into one of two groups. Control group will receive a weekly dose of fluconazole 150mg orally with placebo (Microcrystalline Cellulose USP/NF capsule) on the other days, for a total period of 12 weeks. Patients will complete a questionnaire grading their symptoms and objective signs (erythema, oedema, fissuring, distribution, discharge) will be assessed by 2 independent blinded doctors. Date of menstrual cycle will be recorded. Patients will be reviewed at 6 weeks of treatment. Response to treatment will be re-assessed using the same criteria. At week 12, all patients will undergo repeat clinical examination, questionnaire and blood tests. Those whose symptoms have resolved may continue on 50mg fluconazole twice per week, as an ongoing maintenance dose. These patients will be reassessed using all criteria at 3.6 and 12 months follow up.
The strategy used to monitor adherence to the intervention will be counting and documenting patient's drug tablet return.
Control group
Active

Outcomes
Primary outcome [1] 292997 0
Presence of chronic vulvovaginal candidiasis symptoms.
This will be assessed by patients completing a questionnaire (including Dermatology Life Quality Index) grading their symptoms and objective signs (erythema, oedema, fissuring, distribution, discharge) will be assessed by 2 independent blinded doctors. Date of menstrual cycle will be recorded.
Timepoint [1] 292997 0
6 weeks
Primary outcome [2] 293690 0
Presence of chronic vulvovaginal candidiasis symptoms.
This will be assessed by patients completing a questionnaire (including Dermatology Life Quality Index) grading their symptoms and objective signs (erythema, oedema, fissuring, distribution, discharge) will be assessed by 2 independent blinded doctors. Date of menstrual cycle will be recorded.
Timepoint [2] 293690 0
12 weeks
Secondary outcome [1] 310103 0
Presence of chronic vulvovaginal candidiasis symptoms.
This will be assessed by patients completing a questionnaire (including Dermatology Life Quality Index) grading their symptoms and objective signs (erythema, oedema, fissuring, distribution, discharge) will be assessed by 2 independent blinded doctors. Date of menstrual cycle will be recorded.
Timepoint [1] 310103 0
12 months
Secondary outcome [2] 311598 0
Presence of deranged Liver Function Tests (LFT) after treatment with fluconazole
Timepoint [2] 311598 0
12 weeks

Eligibility
Key inclusion criteria
Female
18 years and older
Premenopausal
Chronic vulvovaginal candidiasis as per diagnostic criteria*
Willingness to give written informed consent and willingness to participate and comply with the study


The diagnostic criteria established are:
Diagnostic: One major + 5 minor criteria
Presumptive: One major + 3-4 minor criteria

Major Criterion:
- Chronic non-erosive, nonspecific vulvovaginitis

Minor Criteria:
- Positive vaginal swab either on presentation or in the past
- Soreness
- Cyclicity
- Dyspareunia
- Previous response to antifungal therapy (even if incomplete)
- Exacerbation with antibiotics
- Swelling
- Discharge
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are pregnant, lactating, or who are planning to become pregnant
Patients with a history of hypersensitivity to fluconazole
Patients with severe renal dysfunction
Patients with liver disease
Patients who are clinically menopausal

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients with a diagnosis of chronic vulvovaginal candidiasis will be identified through the vulval dermatology clinic at Royal North Shore Hospital. Those who fulfill all inclusion criteria and no exclusion criteria will be invited to take part in the study.

Once informed consent has been obtained, a visual analogue scale (VAS) of the patient’s Chronic Vulvovaginal Candidiasis (CVVC) will be performed, as well as a low vaginal swab and baseline blood tests (full blood count, electrolytes/urea/creatinine, liver function tests). Patients will also be asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. If the blood tests return within normal limits, the patient may commence the study.
Patients will be randomized into one of two groups: Group A will take one 50mg fluconazole capsule daily, and Group B will take one 150mg capsule weekly with placebo capsules on the other days. The method of allocation concealment using numbered containers to randomise the two groups.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
2/01/2015
Actual
17/03/2015
Date of last participant enrolment
Anticipated
Actual
26/10/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2909 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 2910 0
Royal Hospital for Women - Randwick
Recruitment hospital [3] 3211 0
Skin and Cancer Foundation Australia (Westmead) - Westmead
Recruitment postcode(s) [1] 8634 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [2] 8635 0
2031 - Randwick
Recruitment postcode(s) [3] 8990 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 289827 0
Other Collaborative groups
Name [1] 289827 0
Australasian College of Dermatologists
Country [1] 289827 0
Australia
Funding source category [2] 289828 0
Commercial sector/Industry
Name [2] 289828 0
Bayer Australia
Country [2] 289828 0
Australia
Funding source category [3] 289829 0
Other Collaborative groups
Name [3] 289829 0
MedicineToday
Country [3] 289829 0
Australia
Primary sponsor type
Hospital
Name
Royal North Shore Hospital
Address
Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 288519 0
University
Name [1] 288519 0
University of Sydney
Address [1] 288519 0
The University of Sydney
NSW 2006
Australia
Country [1] 288519 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291561 0
Northern Sydney Local Health District (NSLHD) Human Research Ethics Committee (HREC)
Ethics committee address [1] 291561 0
Royal North Shore Hospital
Reserve Road, ST LEONARDS NSW 2065
Ethics committee country [1] 291561 0
Australia
Date submitted for ethics approval [1] 291561 0
30/09/2013
Approval date [1] 291561 0
04/12/2013
Ethics approval number [1] 291561 0
1309-282M

Summary
Brief summary
Patients with a diagnosis of chronic vulvovaginal candidiasis will be identified through the vulval dermatology clinic at Royal North Shore Hospital. Those who fulfill all inclusion criteria and no exclusion criteria will be invited to take part in the study.

Once informed consent has been obtained, a visual analogue scale (VAS) of the patient’s CVVC will be performed, as well as a low vaginal swab and baseline blood tests (full blood count, electrolytes/urea/creatinine, liver function tests). Patients will also be asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. If the blood tests return within normal limits, the patient may commence the study.
Patients will be randomized into one of two groups: Group A will take one 50mg fluconazole capsule daily, and Group B will take one 150mg capsule weekly with placebo capsules on the other days.

Patients will return after 6 weeks and the VAS and DLQI will be repeated.

After another 6 weeks, the VAS, DLQI and the blood tests will be repeated. Those who have had significant improvement may continue in the open-label extension and be treated with one 50mg tablet twice per week. Those who have not improved will undergo further investigation within the vulval dermatology clinic.

At each visit, patients will be asked about any potential side-effects or adverse events.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50886 0
A/Prof Gayle Fischer
Address 50886 0
PO Box 4028, Royal North Shore LPO, St Leonards, NSW 2065
Country 50886 0
Australia
Phone 50886 0
+61 (02) 9462 9656
Fax 50886 0
+61 (02) 9462 9095
Email 50886 0
[email protected]
Contact person for public queries
Name 50887 0
Dr Andrew Lee
Address 50887 0
PO Box 4028, Royal North Shore LPO, St Leonards, NSW 2065
Country 50887 0
Australia
Phone 50887 0
+61 (02) 9462 9657
Fax 50887 0
+61 02) 9462 9095
Email 50887 0
[email protected]
Contact person for scientific queries
Name 50888 0
Dr Andrew Lee
Address 50888 0
PO Box 4028, Royal North Shore LPO, St Leonards, NSW 2065
Country 50888 0
Australia
Phone 50888 0
+61 (02) 9462 9657
Fax 50888 0
+61 02) 9462 9095
Email 50888 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTreatment for recurrent vulvovaginal candidiasis (thrush).2022https://dx.doi.org/10.1002/14651858.CD009151.pub2
N.B. These documents automatically identified may not have been verified by the study sponsor.